Effects of growth hormone and insulin-like growth factor I on opsonin receptor expression on local and systemic phagocytes in a lethal peritonitis model.
OBJECTIVE
To investigate the effects of pretreatment with growth hormone (GH) and insulin-like growth factor I (IGF-I) on phagocyte exudation and bacterial clearance, focusing on CD11b and CD32/CD16 expression on local and systemic phagocytes, in a lethal peritonitis model.


METHODS
Prospective randomized experimental study.


METHODS
Research laboratory in a university hospital.


METHODS
Balb/c mice (n = 21).


METHODS
Mice were challenged intraperitoneally with 1 x 10(8) Escherichia coli, after 6 days of pretreatment with saline (control), GH (4.8 mg/kg/day), or IGF-I (24 mg/kg/day). Samples were harvested at 4 hrs after the challenge.


RESULTS
Viable bacterial counts in peritoneal lavage fluid (PLF) and blood were determined. Peritoneal exudative cells and peripheral blood leukocytes were counted and analyzed for receptor expressions by flow cytometry. GH reduced viable bacterial counts in PLF, as compared with the saline control. GH (three-fold) and IGF-I (two-fold) increased the number of peritoneal exudative neutrophils (PENs), as compared with the saline control. The number of PENs showed an inverse correlation with PLF viable bacterial counts. By contrast, there were no differences in peripheral blood neutrophil (PN) counts among the three groups, nor was there a correlation between PN and PEN counts. CD11b expression was greater on PENs than on PNs in all three groups. CD11b expression on PNs did not differ among the three groups. However, GH increased CD11b expression on PENs, as compared with saline and IGF-I, and this expression showed a positive correlation with PEN numbers and an inverse correlation with PLF viable bacterial counts. CD11b expression on peritoneal macrophages and peripheral blood monocytes did not differ among the three groups. There were no differences in phagocyte CD32/CD16 expression among the three groups.


CONCLUSIONS
GH pretreatment enhanced CD11b expression on PENs, but not PNs, possibly in association with enhanced neutrophil recruitment, phagocytosis, and bacterial elimination by PENs, without activation of PNs. GH prophylaxis may be useful for reducing the frequency rate and severity of septic complications, via modulation of CD11b expression on local and systemic neutrophils.
Inoue
T
T
Department of Surgery I, University of Tokyo, Japan.
Saito
H
H
Tsuno
N
N
Fukatsu
K
K
Lin
M T
MT
Inaba
T
T
Han
I
I
Furukawa
S
S
Ikeda
S
S
Matsuda
T
T
Muto
T
T
D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D016177:Macrophage-1 Antigen / Q000032:analysis / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009895:Opsonin Proteins / Q000187:drug effects* / Q000276:immunology; D010538:Peritonitis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D010586:Phagocytes / Q000187:drug effects* / Q000276:immunology; D011446:Prospective Studies; D011897:Random Allocation; D017452:Receptors, IgG / Q000032:analysis / Q000187:drug effects; D011971:Receptors, Immunologic / Q000187:drug effects* / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors
D016177:Macrophage-1 Antigen; D009895:Opsonin Proteins; D017452:Receptors, IgG; D011971:Receptors, Immunologic; C091196:opsonin receptor; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone